Numerous studies in adult rats and mice have demonstrated that chronic administration of narcotics can alter the ability of the hepatic microsomal drug metabolizing enzymes to catalyze the biotransformation of various substrates. We recently observed that perinatal exposure to methadone during gestation and suckling changed the developmental pattern of hepatic microsomal cytochrome c reductase activity in rat pups. Furthermore, the hexobarbital sleeping time, which in adult rats correlates under certain circumstances with hepatic drug metabolism, was significantly shorter in pups exposed perinatally to methadone than in control pups of similar age. Extrapolation of the rodent data to man suggests that infants born to women who take methadone may metabolize drugs differently than normal infants. The objective of the proposed research is to study the biochemical and morphological effects of perinatal exposure to narctics (methadone, morphine, heroin, and l-alpha acetymthadol) on the liver of developing rats. Studies will focus on the development of the drug metabolizing enzymes in microsomes isolated from the livers of rats at various postnatal ages following exposure to narcotics in utero (i.e. placental transport) and/or through the mother's milk. Biochemical studies will be correlated with morphological studies. The aim of this project is to evaluate the extent to which hepatic drug metabolism is altered by perinatal exposure to narcotics and to relate these findings, where possible, to clinical medicine.